Development 2019 146: dev179556 doi: 10.1242/dev.179556 Published 2 September 2019

Stefanie G. Wohl

Department of Biological Structure, University of Washington, School of Medicine, Seattle, WA 98195, USADepartment of Biological and Vision Sciences, The State University of New York, College of Optometry, New York, NY 10036, USA

ABSTRACT

Müller glial cells (MG) generate retinal progenitor (RPC)-like cells after injury in non-mammalian species, although this does not occur in the mammalian retina. Studies have profiled gene expression in these cells to define genes that may be relevant to their differences in neurogenic potential. However, less is known about differences in micro-RNA (miRNA) expression. In this study, we compared miRNAs from RPCs and MG to identify miRNAs more highly expressed in RPCs, and others more highly expressed in MG. To determine whether these miRNAs are relevant to the difference in neurogenic potential between these two cell types, we tested them in dissociated cultures of MG using either mimics or antagomiRs to increase or reduce expression, respectively. Among the miRNAs tested, miR-25 and miR-124 overexpression, or let-7 antagonism, induced Ascl1 expression and conversion of ∼40% of mature MG into a neuronal/RPC phenotype. Our results suggest that the differences in miRNA expression between MG and RPCs contribute to their difference in neurogenic potential, and that manipulations in miRNAs provide a new tool with which to reprogram MG for retinal regeneration.

Grants and financial support provided by the National Eye Institute (NEI R01EY021482 to T.A.R.), by the Deutsche Forschungsgemeinschaft (Wo 2010/1-1), by The State University of New York Empire Innovation Program (1706 to S.G.W.) and by the Foundation Fighting Blindness (TA-RM-0614-0650-UWA to T.A.R.). T.A.R. also acknowledges support from the Paul G. Allen Family Foundation Distinguished Investigator fund. Deposited in PMC for release after 12 months.

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